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Natural Killer Cells (natural + killer_cell)
Terms modified by Natural Killer Cells Selected AbstractsExogenous IL-15 in Combination With IL-15R, Rescues Natural Killer Cells From Apoptosis Induced by Chronic Alcohol ConsumptionALCOHOLISM, Issue 3 2009Hui Zhang Background:, Chronic alcohol consumption reduces the percentage and number of peripheral natural killer (NK) cells in mice and in humans. The underlying mechanism for these changes is only partly known. We recently found that chronic alcohol consumption inhibits NK cell release from the bone marrow (BM) and that this is associated with a decrease in splenic NK cells. The number of peripheral NK cells is tightly controlled by homeostatic proliferation. It is not known whether this mechanism is initiated in response to the reduction in splenic NK cells, or if so, why the steady state levels of NK cells are not restored. Methods:, To examine this mechanism, female C57BL/6 mice were given 20% w/v alcohol in the drinking water for 3 months. NK cell proliferation and apoptosis were determined before and after treatment with IL-15 alone or combined with its alpha receptor. Results:, Chronic alcohol consumption invoked homeostatic proliferation of splenic NK cells in an attempt to return NK cells to normal levels; however, this did not happen due to enhanced apoptosis of NK cells relative to proliferation. Chronic alcohol consumption decreased IL-15 producing cells in the spleen but not in the BM. The numbers of NK cells in the alcohol-consuming mice returned to normal levels in the spleen and were higher than normal in the BM after 2 daily injections of IL-15; however, the enhanced rate of apoptosis due to alcohol consumption was not decreased in the spleen or BM. Combined IL-15 and IL-15R, treatment decreased apoptosis of NK cells from alcohol-consuming mice to levels similar to untreated water-drinking mice and greatly increased the percentage and number of NK cells in both the spleen and BM. Conclusion:, Chronic alcohol consumption causes a self-unrecoverable loss of NK cells in the spleen by compromising NK cell release from the BM and enhancing splenic NK cell apoptosis that can be reversed with IL-15/IL-15R, treatment. [source] Alcohol Suppresses IL-2,Induced CC Chemokine Production by Natural Killer CellsALCOHOLISM, Issue 9 2005Ting Zhang Background: Natural killer (NK) cells are a critical component of the host innate immune system. We investigated whether alcohol impairs NK cell function, particularly production of CC chemokines induced by interleukin (IL)-2, the natural ligands for CCR5 receptor. Methods: Primary NK cells and NK cell line (YTS) were cultured with or without alcohol (10 to 80 mM) for three hours. The culture supernatants were then harvested and used to treat human peripheral blood monocyte-derived macrophages and a HeLa cell line, which expresses CD4, CCR5, and CXCR4 receptors (MAGI cells). CC chemokine expression by YTS and primary NK cells treated with or without alcohol was analyzed with the real-time RT-PCR and ELISA. Ca2+i and Western blot assays were used to determine calcium-mediated intracellular signaling pathway and NF-,B p65 expression. HIV strains (Bal and UG024) were used to infect macrophages and MAGI cells. In addition, ADA (macrophage-tropic strain) and murine leukemia virus (MLV) envelope-pseudotyped HIV infection was carried out in macrophages. HIV infectivity was determined by HIV reverse transcriptase (RT) and ,-galactosidase activity assays. Results: Alcohol inhibited IL-2,induced CC chemokine (CCL3 and CCL4) expression by NK cells. Functional tests demonstrated that this reduced expression of CC chemokines was associated with diminished anti-HIV ability of NK cells. Alcohol also reduced the ability of NK cells to response to CCL3-mediated chemotaxis. Alcohol inhibited IL-2,induced NF-,B p65 protein expression and calcium mobilization by NK cells. Conclusions: Alcohol, through the inhibition of IL-2,induced NF-,B p65 protein expression and intracellular calcium mobilization, suppressed NK cell production of CC chemokines. This suppression of CC chemokine production was associated with diminished anti-HIV activity of NK cells. Thus, by inhibiting NK cell,mediated innate immunity against HIV, alcohol consumption may have a cofactor role in the immunopathogenesis of HIV disease. [source] SHORT COMMUNICATION: CD3, CD56+ CD16+ Natural Killer Cells and Improvement of Pregnancy Outcome in IVF/ICSI Failure After Additional IVIG-TreatmentAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Lothar Heilmann Citation Heilmann L, Schorsch M, Hahn T. CD3, CD56+ CD16+ Natural killer cells and improvement of pregnancy outcome in IVF/ICSI failure after additional IVIG-treatment. Am J Reprod Immunol 2010; 63: 263,265 Problem, The purpose of this retrospective, observational study was to investigate whether additional treatment with intravenous immunglobulin (IVIG) increased the rate of successful pregnancies after repeated implantation failure (RIF). The retrospective data were compared with data of patients without IVIG-therapy from the meta-analysis of Clark et al. Method of study, A total of 188 women with 226 treatment cycles between 2007 and 2009 were evaluated for IVIG therapy. The percentage of NK cells was measured two times before a new embryo transfer (only women with NK cell percentages >12% were included) and after embryo transfer at a positive pregnancy test. Results, In comparison with the meta-analysis of Clark et al., we observed a pregnancy rate of 50.5%, an implantation rate of 21% and a miscarriage rate of 16.8%. In 42%/IVIG- patient or 34.9%/embryo transfer, we observed a live born baby. The live born rate per embryo was 16.6%. In accordance with the study of Kwak et al., we indicate a decrease in the NK cells in patients with improved pregnancy outcome. Conclusion, In a subgroup of RIF-patients with high level of CD56+ CD16+ NK-cells the additional application of IVIG leads to a favourable pregnancy outcome. [source] ORIGINAL ARTICLE: Comparative Analysis of Peripheral Natural Killer Cells in the Two Phases of the Ovarian CycleAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Ageliki Pantazi Problem Changes in endometrial Natural Killer (NK) cells during the luteal phase of the ovarian cycle are important in initiating/maintaining a subsequent pregnancy. In the present study it was investigated whether during the menstrual cycle changes occur also in peripheral blood (PB) NKs. Method of study Blood samples during the follicular and the luteal phase were collected from 30 women without fertility problems. Samples were analyzed by flow-cytometry for: (1) NK cells (CD3,CD16+CD56+) and (2) intracellular production of interferon-, (IFN-,) by NK cells. For the comparison and correlation of the two populations between the two phases, Wilcoxon signed-rank test and Spearman's Coefficient were used. Results The differences in percentages of CD3,CD16+CD56+ cells and that of CD3,CD16+CD56+/IFN-,+ cells between the follicular and the luteal phase were not statistically significant (10.61 ± 5.11 versus 9.76 ± 4.57 and 6.48 ± 7.90 versus 7.30 ± 6.77, respectively, P > 0.05). The correlation between the two variables (NK% and NK/IFN-,%) was weakly positive (P = 0.07) only in the follicular phase. Conclusion The study did not reveal menstrual cycle-depended changes in PB NK cells. Thus, a suggestion to measure these cells in a specific phase of the cycle in order to predict the outcome of a subsequent pregnancy in women with fertility problems is objected. [source] ORIGINAL ARTICLE: A High Dose of Intravenous Immunoglobulin Increases CD94 Expression on Natural Killer Cells in Women with Recurrent Spontaneous AbortionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Shigeki Shimada Problem, A high dose of intravenous immunoglobulin (HIVIg) therapy is effective in various diseases such as autoimmune diseases, and also is expected to have efficacy in recurrent spontaneous abortion (RSA). The aim of this study was to understand immunological mechanisms of this therapy. Method of study, By flowcytometric analyses, we examined phenotypic changes of a variety of immunological cells including natural killer (NK) cells, cytotoxic T cells, regulatory T cells and macrophages in peripheral blood of RSA women with HIVIg therapy (n = 8). Results, Expression percentages of inhibitory CD94 on NK cells significantly (P = 0.01) increased after the therapy (58.8 ± 21.4% versus 71.0 ± 17.6%). Conclusion, Mechanisms of possible efficacy of HIVIg therapy for RSA may include enhancement of CD94 expression and subsequent suppression of NK cell cytotoxicity. [source] ERRATUM: Women with Pre-Eclampsia have an Altered NKG2A and NKG2C Receptor Expression on Peripheral Blood Natural Killer CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Nora Bachmayer No abstract is available for this article. [source] ORIGINAL ARTICLE: Women with Pre-Eclampsia Have an Altered NKG2A and NKG2C Receptor Expression on Peripheral Blood Natural Killer CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009Nora Bachmayer Problem, Preeclampsia, a pregnancy disorder, is associated with exaggerated inflammation and increased serum monokines. Uterine natural killer (NK) cells are implicated in preeclampsia pathology, but little is known regarding peripheral NK cells in the disease. Method of Study, We examined blood NK cells at delivery in women with preeclampsia, in healthy pregnant women and in healthy non-pregnant blood donors as a reference. Results, Although the percentages of both NKG2A- and NKG2C-positive NK cells were normal in preeclamptic women, the levels of NKG2A and NKG2C on NK cells were significantly up-regulated in these women. In vitro stimulation of PBMCs from healthy pregnant women and blood donors with monokines resulted in increased percentage of NKG2A+ NK cells and increased NKG2A levels, while levels of NKG2C were decreased. Conclusions, Our results suggest that the peripheral NK-cell pool is skewed in preeclampsia and possibly under the influence of monokines like interleukin (IL)-15 and IL-12. [source] ORIGINAL ARTICLE: Timed Sexual Intercourse Facilitates the Recruitment of Uterine CD56bright Natural Killer Cells in Women with InfertilityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Hidetaka Kimura Problem, The aim of this study was to investigate the influence of sexual intercourse on uterine NK cell subsets. Method of study, Mid-secretory endometrial samples obtained from 56 women were submitted for flow cytometric analysis. Basal body temperature was used to determine the day of ovulation. A total of 27 women had sexual intercourse before ovulation (pre-ovulation group) and eight women had only after ovulation (post-ovulation group) without any contraceptive devices. A total of 21 women did not have sexual intercourse during the experimental cycle (abstinence group). Endometrial NK cells were analyzed for the expression of CD16 and CD56 using 3-color flow cytometry. Results, CD16,/CD56bright cells were markedly increased in the pre-ovulation group as compared with that of the post-ovulation group (P < 0.01) and the abstinence group (P < 0.01). CD16+/CD56dim cells were significantly decreased in the pre-ovulation group as compared with that of the post-ovulation group (P < 0.01) and the abstinence group (P < 0.05). Conclusion, It is suggested that seminal plasma participates in the recruitment of CD56bright NK cells into endometrium. [source] ORIGINAL ARTICLE: Mifepristone as an Anti-Implantation Contraceptive Drug: Roles in Regulation of Uterine Natural Killer Cells during Implantation PhaseAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Hong-Xia Zhu Problem, To investigate the immunological mechanism of low-dose mifepristone acting as a contraceptive at the level of the endometrium. Method of study, Endometrial explants were cultured in vitro with or without mifepristone treatment for 24 hr. Some tissues were fixed and immunostained for CD56, while other tissues were dissociated and cells analysed by three colour flow cytometry for CD3, CD56 and CD16. Results and conclusion, Results showed a significant increase in the number of CD56+ natural killer (NK) cells and the percentages of CD3, CD56+ CD16, NK cell subset in the tissue treated with mifepristone, while the percentage of CD3, CD56+ CD16+ NK cell subset remained unaffected. It shows that low-dose mifepristone increases the number of CD56+ NK cells and the percentage of CD3, CD56+ CD16, NK subset in receptive endometrium and provides new insights into the immunological mechanism of low-dose mifepristone as an anti-implantation contraceptive drug. [source] REVIEW ARTICLE: Clinical Implication of Natural Killer Cells and ReproductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2008Joanne Kwak-Kim The regulation of natural killer (NK) cells in the peripheral blood and endometrial layers has been associated with reproductive immunopathology such as recurrent spontaneous abortions (RSA), infertility of implantation failures, or pre-eclampsia. The placenta has a complex anatomical structure and different subsets of NK cells with various functional roles can directly interact with trophoblasts. NK cell subpopulations and their functions, putative roles of NK cells in peripheral blood and endometrium are reviewed in relation to RSA and infertility. An increase in NK cell numbers and /or activity in pre- or post-conceptional period in women with RSA or infertility with multiple implantation failures are a significant clinical concern. In addition, immuno-phenotypic characteristics of NK cells in these women support the changes for their increased activity status. Further studies are needed to explore underlying mechanism of NK cells in RSA, infertility, and other reproductive immunopathologies. Possible neurological and hormonal control of NK cells and NK cell interaction with various leukocyte populations need further investigation in women with reproductive failures. [source] Natural Killer Cells and the Immune Response in Solid Organ TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010W. Van Der Touw Natural killer (NK) cells have been characterized classically for their cytotoxicity against pathogen infected or stressed cells as well as for their role in monitoring the expression of self MHC I. However, the participation of NK cells in solid organ transplantation (SOT) is poorly defined due to conflicting clinical and animal model data. Preclinical models have shown that NK cells exacerbate T-cell allogeneic responses during rejection, but can also promote tolerance induction under immunosuppressive conditions. Further, while protocols such as costimulatory blockade effectively induce tolerance by blocking T-cell activation and promoting Treg generation, how such regimens regulate other innate and adaptive immune cells, including NK cells, is incomplete. This review examines NK cells and the regulation of their effector functions in SOT. [source] Remodeling of the actin cytoskeleton of target hepatocytes and NK cells during induction of apoptosisCYTOSKELETON, Issue 2 2001W. Marty Blom Abstract Natural Killer cells are immune cells that recognize and eliminate altered and non-self cells from the circulation. To study the interaction between NK cells and target cells, we set up an experimental system consisting of rat Interleukin-2 activated Natural Killer cells (A-NK cells) and rat hepatocytes with a masked Major Histocompatibility Complex (MHC). The masking of the MHC induces recognition of the hepatocytes by the NK cells as non-self. We showed that in vitro apoptosis is rapidly induced in the hepatocytes [Blom et al., 1999] after co-incubation with A-NK cells. Now we describe the morphological changes that occur during and after interaction of A-NK cells with hepatocytes. Confocal laser scanning microscopy showed that the actin cytoskeleton of the NK cells was remodeled during attack of hepatocytes. Some NK cells were in close contact with the hepatocytes while others had formed actin-containing dendrites of varying length that made contact with the hepatocytes. However, dendrite formation is not obligatory for induction of apoptosis because cells that were unable to form these did induce FAS-dependent apoptosis in hepatocytes. Apparently both direct as well as distant contact resulted in apoptosis. Formation of the dendrites was calcium-dependent as EGTA largely prevented it. Importantly, chelation of the calcium also suppressed killing of the hepatocytes. Within 1 h after addition of the A-NK cells, morphological changes in hepatocytes that are characteristic of apoptosis, such as the formation of apoptotic bodies and fragmented nuclei, became apparent. Specifically, the actin cytoskeleton of the hepatocytes was remodeled resulting in the formation of the apoptotic bodies. Inhibition of caspase activity by z-Val-Ala-DL-Asp-fluoromethylketone (100 ,M) partly protected against the rearrangement of the actin filaments in the hepatocytes. Cell Motil. Cytoskeleton 49:78,92, 2001. © 2001 Wiley-Liss, Inc. [source] Natural killer cell-based immunotherapy in cancer: current insights and future prospectsJOURNAL OF INTERNAL MEDICINE, Issue 2 2009T. Sutlu Abstract. As our understanding of the molecular mechanisms governing natural killer (NK) cell activity increases, their potential in cancer immunotherapy is growing increasingly prominent. This review analyses the currently available preclinical and clinical data regarding NK cell-based immunotherapeutic approaches in cancer starting from a historical background and an overview of molecular mechanisms taking part in NK cell responses. The status of NK cells in cancer patients, currently investigated clinical applications such as in vivo modulation of NK cell activity, ex vivo purification/expansion and adoptive transfer as well as future possibilities such as genetic modifications are discussed in detail. [source] Natural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] Natural killer cells become tolerogenic after interaction with apoptotic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2010Wai Po Chong Abstract NK cells are effectors in innate immunity and also participate in immunoregulation through the release of TGF-,1 and lysis of activated/autoreactive T cells. Apoptotic cells (AC) have been shown to induce tolerogenic properties in innate immune cells, including macrophages and dendritic cells, but not NK cells. In this study, we demonstrated that after interaction with AC, NK cells released TGF-,1, which in turn suppressed the production of IFN-, by NK cells upon IL-12 and IgG activation. We further identified phosphatidylserine as a potential target on AC for the NK cells, as phosphatidylserine could stimulate NK cells to release TGF-,1, which in turn suppressed CD4+ T-cell proliferation and activation. Moreover, AC-treated NK cells displayed cytotoxicity against autologous-activated CD4+ T cells by upregulating NKp46. This lysis occurred in part through the NKp46-vimentin pathway, as activated CD4+ T cells expressed vimentin on the cell surface and blocking of vimentin or NKp46, but not other NK-cell receptors, significantly suppressed the NK-cell cytotoxicity. We report here a novel interaction between NK cells and AC, resulting in the tolerogenic properties of NK cells required for immune contraction. [source] Natural killer cells in infection and inflammation of the lungIMMUNOLOGY, Issue 2 2009Fiona J. Culley Summary The lungs are a major site of entry of pathogens into the body and thus require rapid and effective innate responses to prevent pathogens establishing infection and to limit their spread. Additionally, the immune response in the lung must be tightly regulated such that pathogens are cleared, but immunopathology and chronic inflammation are prevented. In this review, I consider the role of natural killer (NK) cells in pulmonary infection and inflammation, specifically their contributions to influenza, tuberculosis, asthma and chronic obstructive pulmonary disease (COPD), which are major causes of morbidity and mortality world-wide. Despite evidence of the importance of NK cells in these diseases, there are still major gaps in our understanding of how their function is regulated in this unique tissue environment. Understanding how different beneficial and detrimental effector functions of NK cells are triggered will be crucial if NK cells are to be exploited therapeutically in respiratory disease. [source] Natural killer cells: integrating diversity with functionIMMUNOLOGY, Issue 4 2009Kuldeep Cheent Summary The key role of natural killer cells in many aspects of the immune response is now being recognized. The last decade has seen an exponential increase in our understanding of the workings of these cells. Receptor diversity is crucial in allowing natural killer cells to respond effectively to a variety of different pathogens. This article reviews aspects of natural killer cell diversity that combine to generate populations of functional natural killer cells that exist within both the individual and throughout the population at large. [source] Natural killer cells suppress full cycle HCV infection of human hepatocytesJOURNAL OF VIRAL HEPATITIS, Issue 12 2008S.-H. Wang Summary., The role of natural killer (NK) cells in controlling hepatitis C virus (HCV) infection and replication has not been fully delineated. We examined NK cell-mediated noncytolytic effect on full cycle HCV infection of human hepatocytes. Human hepatocytes (Huh7.5.1 cells) co-cultured with NK cells or treated with supernatants (SN) from NK cells cultures had significantly lower levels of HCV RNA and protein than control cells. This NK cell-mediated anti-HCV activity could be largely abolished by antibody to interferon-gamma (IFN-,). The investigation of the mechanisms for NK cell-mediated anti-HCV activity showed that NK SN-treated hepatocytes expressed higher levels of IFN-,/, than the control cells. NK SN also enhanced IFN regulatory factor-3 and 7 expression in the hepatocytes. In addition, NK SN enhanced the expression of signal transducer and activator of transcription 1 and 2, the nuclear factors that are essential for the activation of IFN-mediated antiviral pathways. These data provide direct evidence at cellular and molecular levels that NK cells have a key role in suppressing HCV infection of and replication in human hepatocytes. [source] Natural killer cells play divergent roles in shaping the outcome of hepatitis C virus recurrence following liver transplantation,LIVER TRANSPLANTATION, Issue 4 2009Lucy Golden-Mason [source] SHORT COMMUNICATION: CD3, CD56+ CD16+ Natural Killer Cells and Improvement of Pregnancy Outcome in IVF/ICSI Failure After Additional IVIG-TreatmentAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Lothar Heilmann Citation Heilmann L, Schorsch M, Hahn T. CD3, CD56+ CD16+ Natural killer cells and improvement of pregnancy outcome in IVF/ICSI failure after additional IVIG-treatment. Am J Reprod Immunol 2010; 63: 263,265 Problem, The purpose of this retrospective, observational study was to investigate whether additional treatment with intravenous immunglobulin (IVIG) increased the rate of successful pregnancies after repeated implantation failure (RIF). The retrospective data were compared with data of patients without IVIG-therapy from the meta-analysis of Clark et al. Method of study, A total of 188 women with 226 treatment cycles between 2007 and 2009 were evaluated for IVIG therapy. The percentage of NK cells was measured two times before a new embryo transfer (only women with NK cell percentages >12% were included) and after embryo transfer at a positive pregnancy test. Results, In comparison with the meta-analysis of Clark et al., we observed a pregnancy rate of 50.5%, an implantation rate of 21% and a miscarriage rate of 16.8%. In 42%/IVIG- patient or 34.9%/embryo transfer, we observed a live born baby. The live born rate per embryo was 16.6%. In accordance with the study of Kwak et al., we indicate a decrease in the NK cells in patients with improved pregnancy outcome. Conclusion, In a subgroup of RIF-patients with high level of CD56+ CD16+ NK-cells the additional application of IVIG leads to a favourable pregnancy outcome. [source] Inhibition of term decidual NK cell cytotoxicity by soluble HLA-G1AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5-6 2006Tobias G. Poehlmann Objectives, Soluble (s)HLA-G1 is produced by trophoblast cells. Aim was to analyze the capacities and mechanisms of sHLA-G1 to regulate interleukin (IL)-2-induced cytotoxicity of natural killer (NK) cells from human deciduas. Methods, Natural killer cells were isolated from decidual layers of term placentae, stimulated or not with IL-2 and supplemented with various concentrations of recombinant soluble HLA-G1 (sHLA-G1). For NK cell cytotoxicity assays, K562 cells were used as targets. Expression of signal transducer and activator of transcription 3 (STAT3) and perforin was analyzed by Western blotting. Apoptosis was examined by assessment of poly(ADP-ribose) polymerase cleavage. NK cells were analyzed by flow cytometry for IL-2receptor- , (IL-2R,; CD25) and transferrin receptor CD71 expression. Results, Interleukin-2 increases CD71, STAT3, perforin expression and cytotoxic potential of NK cells. Expression of CD71, STAT3 and perforin decreased simultaneously with cytotoxicity and dose-dependently when sHLA-G1 (1.6 ,g/mL,1.6 ng/mL) was added to IL-2 stimulated cultures. sHLA-G1 did not induce apoptosis and CD25 expression was not affected. Conclusion, Interleukin-2R, expression is not controlled by sHLA-G1, but its signal transducer STAT3 as well as several downstream effects, such as perforin expression, proliferation and cytotoxicity. The control of STAT3 bioavailability through sHLA-G1 may be a key regulator of the mentioned effects. [source] Might Wasp Venom Desensitization Induced Th2 to Th1 Shift Cause Pregnancy Failure?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2002UDO R. MARKERT The case of a 28-year-old woman under wasp venom desensitization having a premature birth in her 24th week of pregnancy 16 days after the last injection is described. To test the hypothesis that a special profile of immune cells in the decidua may trigger abortions, placental and decidual tissue sections were stained with antibodies against T cells (CD3), cytotoxic cells (CD8), natural killer cells (CD56), and mast cells, and an in-situ-hybridization was performed for tumor necrosis factor-, (TNF-,). CD56+ Natural killer cells were the dominating population. In earlier analyses of healthy first trimester decidua the percentage of NK cells and T cells was in a similar range, but the CD8:CD3 ratio was only 2.2% in contrast to 27% in the present case. Mast cells, which are known to be able to secrete abortogenic TNF-,, were only detectable in the decidua (10 cells/mm2) and decidua sections were TNF-, positive. Since SIT induces a shift of the interleukin and functional profile from a Th2 type towards a Th1 type, and pregnancy is dependent on a Th2 pronounced profile, SIT may trigger abortions or immature births. This is supported by the present results and might have happened in this case. [source] Putting the natural killer cell in its placeIMMUNOLOGY, Issue 1 2006Geraldine M. O'Connor Summary Natural killer (NK) cells were originally described as ,null' lymphocytes, but we have increasing evidence of their role in recognizing pathogen, and our knowledge of NK cell receptors continues to expand exponentially. Human NK cells have many receptors for human leucoctye antigen (HLA) class I. These killer immunoglobulin-like receptors (KIRs) and CD94/NKG2 receptors can signal in both positive and negative ways to regulate NK cell functions. The inhibitory receptors are the best characterized, but even in these cases much of their functional biology remains elusive. In this review, some recent advances in terms of the three-immunoglobulin (3Ig)-domain KIRs are discussed. Natural cytotoxicity receptors (NCRs) are among the activatory receptors found on NK cells. While pathogen ligands for these receptors have been described, endogenous ligands remain elusive. NCRs and NKG2D, a receptor for stress-induced antigens, appear to play complementary functional roles in terms of NK cell activation. More recently described on NK cells are the Toll-like receptors. In particular, these receptors of the innate immune system allow NK cells to directly sense pathogen, and their ligation on accessory cells indirectly activates NK cells through cytokine production. It is becoming clear that none of these receptor systems functions in isolation and that it is the sum of the signals (which will reflect the pathogenic situation), in addition to the cytokine milieu, that will direct NK cell activation. The resulting cytotoxicity, cytokine production and direct cell,cell regulatory interactions with other cells of the immune system, for example dendritic cells, ultimately determine the role of the NK cell in the context of an overall immune response. [source] Leptin and Cellular and Innate Immunity in Abstinent Alcoholics and ControlsALCOHOLISM, Issue 11 2003Sarosh J. Motivala Background: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity. Methods: Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2),stimulated NK activity, and concanavalin A,stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n= 27) and age- and gender-matched controls (n= 34). Results: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p= 0.055). In the total sample, leptin predicted NK activity (,= 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n= 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone. Conclusions: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases. [source] Liver-infiltrating CD56 positive T lymphocytes in hepatitis C virus infectionLIVER INTERNATIONAL, Issue 5 2000Kenji Yonekura Abstract:Aim: Hepatitis C virus (HCV) is a major cause of post-transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus-specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV-infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56+ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH-C). Material and Methods: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH-C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver-infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. Results: The CD56+ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly ,,-TCR. There was a correlation between the ratio of CH-C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. Conclusion: The correlation between CD56+ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver-infiltrating CD56+ T lymphocytes play an important pathologic role in hepatocellular injury in CH-C. [source] The treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2001O. H. Nielsen The thioguanine derivative, azathioprine, is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6-mercaptopurine have been used in the treatment of inflammatory bowel disease, i.e. ulcerative colitis and Crohn's disease, for more than 30 years. However, widespread use of azathioprine or 6-mercaptopurine in inflammatory bowel disease is of more recent origin, the primary reason being a long-standing debate on the efficacy of these agents in inflammatory bowel disease. Both drugs are slow acting, which is why clinical efficacy cannot be expected until several weeks or even months of treatment have elapsed. Consequently, azathioprine and 6-mercaptopurine have no place as monotherapy in the treatment of acute relapsing inflammatory bowel disease. Today, azathioprine and 6-mercaptopurine are the most commonly used immunomodulatory drugs in the treatment of inflammatory bowel disease. Their clinical effects are probably identical, although their exact mode of action is still unknown. The mode of action of azathioprine is thought to be multifactorial, including conversion to 6-mercaptopurine (which acts as a purine antimetabolite), possible blockade of thiol groups by alkylation, inhibition of several pathways in nucleic acid biosynthesis (preventing proliferation of cells involved in the determination and amplification of the immune response) and damage to DNA through the incorporation of thiopurine analogues. However, 6-thioguanine nucleotides may accumulate in toxic doses in myeloid precursor cells, resulting in life-threatening myelosuppression. Azathioprine and 6-mercaptopurine are further known to alter lymphocyte function, reduce the number of lamina propria plasma cells and affect natural killer cell function. The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease. [source] Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosisPEDIATRIC BLOOD & CANCER, Issue 6 2008Carl E. Allen MD Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal condition characterized by a pathologic inflammation. The diagnostic criteria for HLH include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, abnormal natural killer cell (NK cell) functional assay, elevated soluble IL-2R, level, and elevated ferritin level (>500 µg/L). Institution of timely therapy in these critically ill patients may be delayed by difficulties establishing the diagnosis. NK cell functional assay and soluble IL-2R, level may require send-out to a specialized lab. However, ferritin level is available on a same-day basis at most institutions. In this study, we examined the utility of quantitative ferritin levels in diagnosing HLH. Procedure All patients with ferritin values >500 µg/L obtained at Texas Children's Hospital between January 10, 2003 and January 10, 2005 were identified. Patient charts were reviewed for ferritin levels and hospital course. Results During the study interval, 330 patients had ferritin levels >500 µg/L. Ten of the 330 patients were diagnosed with HLH. A ferritin level over 10,000 µg/L was 90% sensitive and 96% specific for HLH. Another diagnostic category with significantly elevated ferritin level was illness of unknown cause (n,=,10), and only two of these patients were fully evaluated for HLH. Conclusions Ferritin levels above 10,000 µg/L appear to be specific and sensitive for HLH. In patients without a significant medical history and a new onset of febrile illness with highly elevated ferritin levels, the diagnosis of HLH should be evaluated. Pediatr Blood Cancer 2008;50:1227,1235. © 2007 Wiley-Liss, Inc. [source] Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivityCONTACT DERMATITIS, Issue 5 2007Jeppe Madura Larsen Background:, The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. Objectives:, To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. Patients/Methods:, Mice were sensitized and/or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. Results:, The presented method can be applied to evaluate the effect of different contact allergens on various cell populations of the immune system. Conclusions:, Our study support recent findings that several cell types seem to be involved in CHS. [source] Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitroEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007K. Hoetzenecker Abstract Background Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms. Materials and methods/results CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFN,), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and Fc,RIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions. Conclusions We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response. [source] Intrasplenic trafficking of natural killer cells is redirected by chemokines upon inflammationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Claude Grégoire Abstract The spleen is a major homing site for NK cells. How they traffic to and within this site in homeostatic or inflammatory conditions is, however, mostly unknown. Here we show that NK cells enter the spleen through the marginal sinus and home to the red pulp via a pertussis toxin-insensitive mechanism. Upon inflammation induced by poly(I:C) injection or mouse cytomegalovirus infection, many NK cells left the red pulp while others transiently entered the white pulp, predominantly the T cell area. This migration was dependent on both CXCR3 and CCL5, suggesting a synergy between CXCR3 and CCR5, and followed the path lined by fibroblastic reticular cells. Thus, the entry of NK cells in the white pulp is limited by the expression of pro-inflammatory chemokines. This phenomenon ensures the segregation of NK cells outside of the white pulp and might contribute to the control of immunopathology. [source] | ||||||||||||||||||||||||||||||||||